macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma
Self-renewal is a crucial property of glioblastoma cells that is enabled by the choreographed functions of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could therefore represent an important step toward developing effective treatments f...
| المؤلفون الرئيسيون: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
Springer Nature
2023
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| _version_ | 1826310691593650176 |
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| author | Nikolic, A Maule, F Bobyn, A Ellestad, K Paik, S Marhon, SA Mehdipour, P Lun, X Chen, H-M Mallard, C Hay, AJ Johnston, MJ Gafuik, CJ Zemp, FJ Shen, Y Ninkovic, N Osz, K Labit, E Berger, ND Brownsey, DK Kelly, JJ Biernaskie, J Dirks, PB Derksen, DJ Jones, SJM Senger, DL Chan, JA Mahoney, DJ De Carvalho, DD Gallo, M |
| author_facet | Nikolic, A Maule, F Bobyn, A Ellestad, K Paik, S Marhon, SA Mehdipour, P Lun, X Chen, H-M Mallard, C Hay, AJ Johnston, MJ Gafuik, CJ Zemp, FJ Shen, Y Ninkovic, N Osz, K Labit, E Berger, ND Brownsey, DK Kelly, JJ Biernaskie, J Dirks, PB Derksen, DJ Jones, SJM Senger, DL Chan, JA Mahoney, DJ De Carvalho, DD Gallo, M |
| author_sort | Nikolic, A |
| collection | OXFORD |
| description | Self-renewal is a crucial property of glioblastoma cells that is enabled by the choreographed functions of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could therefore represent an important step toward developing effective treatments for this universally lethal cancer. Here we uncover an epigenetic axis of self-renewal mediated by the histone variant macroH2A2. With omics and functional assays deploying patient-derived in vitro and in vivo models, we show that macroH2A2 shapes chromatin accessibility at enhancer elements to antagonize transcriptional programs of self-renewal. macroH2A2 also sensitizes cells to small molecule-mediated cell death via activation of a viral mimicry response. Consistent with these results, our analyses of clinical cohorts indicate that high transcriptional levels of this histone variant are associated with better prognosis of high-grade glioma patients. Our results reveal a targetable epigenetic mechanism of self-renewal controlled by macroH2A2 and suggest additional treatment approaches for glioblastoma patients. |
| first_indexed | 2024-03-07T07:55:42Z |
| format | Journal article |
| id | oxford-uuid:3a536d21-7605-43b7-9904-a0e2734ce1b3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:55:42Z |
| publishDate | 2023 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:3a536d21-7605-43b7-9904-a0e2734ce1b32023-08-22T12:03:53ZmacroH2A2 antagonizes epigenetic programs of stemness in glioblastomaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3a536d21-7605-43b7-9904-a0e2734ce1b3EnglishSymplectic ElementsSpringer Nature2023Nikolic, AMaule, FBobyn, AEllestad, KPaik, SMarhon, SAMehdipour, PLun, XChen, H-MMallard, CHay, AJJohnston, MJGafuik, CJZemp, FJShen, YNinkovic, NOsz, KLabit, EBerger, NDBrownsey, DKKelly, JJBiernaskie, JDirks, PBDerksen, DJJones, SJMSenger, DLChan, JAMahoney, DJDe Carvalho, DDGallo, MSelf-renewal is a crucial property of glioblastoma cells that is enabled by the choreographed functions of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could therefore represent an important step toward developing effective treatments for this universally lethal cancer. Here we uncover an epigenetic axis of self-renewal mediated by the histone variant macroH2A2. With omics and functional assays deploying patient-derived in vitro and in vivo models, we show that macroH2A2 shapes chromatin accessibility at enhancer elements to antagonize transcriptional programs of self-renewal. macroH2A2 also sensitizes cells to small molecule-mediated cell death via activation of a viral mimicry response. Consistent with these results, our analyses of clinical cohorts indicate that high transcriptional levels of this histone variant are associated with better prognosis of high-grade glioma patients. Our results reveal a targetable epigenetic mechanism of self-renewal controlled by macroH2A2 and suggest additional treatment approaches for glioblastoma patients. |
| spellingShingle | Nikolic, A Maule, F Bobyn, A Ellestad, K Paik, S Marhon, SA Mehdipour, P Lun, X Chen, H-M Mallard, C Hay, AJ Johnston, MJ Gafuik, CJ Zemp, FJ Shen, Y Ninkovic, N Osz, K Labit, E Berger, ND Brownsey, DK Kelly, JJ Biernaskie, J Dirks, PB Derksen, DJ Jones, SJM Senger, DL Chan, JA Mahoney, DJ De Carvalho, DD Gallo, M macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma |
| title | macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma |
| title_full | macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma |
| title_fullStr | macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma |
| title_full_unstemmed | macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma |
| title_short | macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma |
| title_sort | macroh2a2 antagonizes epigenetic programs of stemness in glioblastoma |
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